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Supra- and infratentorial pediatric ependymomas differ significantly in NeuN, p75 and GFAP expression
Christian Hagel1, András Treszl, Julia Fehlert
1Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. hagel@uke.de
Insights
Pediatric ependymomas show distinct protein expression patterns based on tumor location. Supratentorial tumors had higher neuronal markers, while posterior fossa tumors showed more glial markers, suggesting different origins.
Area of Science:
- Pediatric neuro-oncology
- Tumor biology
- Immunohistochemistry
Background:
- Ependymomas are common pediatric brain tumors, accounting for 8% of intracranial tumors in children under 15.
- Neuronal antigen expression, particularly neurofilament protein light polypeptide (NEFL), is linked to better outcomes in some ependymomas.
- Understanding molecular differences based on tumor location may reveal distinct cellular origins.
Purpose of the Study:
- To investigate differential protein expression in pediatric ependymomas based on tumor location (supratentorial, posterior fossa, spinal).
- To evaluate markers including neurotrophin receptors (TrkA, p75), neuronal markers (NeuN, synaptophysin), glial markers (SOX9, GFAP), and adhesion molecules.
- To correlate protein expression patterns with tumor topography.
Main Methods:
- Retrospective immunohistochemical analysis of 25 pediatric ependymomas (6 supratentorial, 15 posterior fossa, 4 spinal).
- Semi-quantitative and quantitative assessment of protein expression for various markers.
- Comparison of marker expression levels between supratentorial and infratentorial tumors.
Main Results:
- Significantly higher expression of p75 (NGFR) and NeuN (RBFOX3) in supratentorial ependymomas compared to infratentorial tumors.
- Significantly higher expression of GFAP in infratentorial ependymomas.
- Differential expression patterns suggest distinct tumor origins based on location.
Conclusions:
- Immunohistochemical profiles of p75, NeuN, and GFAP differ between supratentorial and infratentorial pediatric ependymomas.
- These findings support the hypothesis of divergent cells of origin for ependymomas based on tumor topography.
- Further validation in larger cohorts is recommended due to the preliminary nature of these results.
Abstract:
Ependymomas comprise 8 % of all intracranial tumors in children <15 years. Recent studies revealed that some supratentorial ependymomas express neuronal antigens and that high expression of neurofilament protein light polypeptide (NEFL) correlates with better clinical outcome. We retrospectively analyzed an expanded panel of proteins in 6 supratentorial, 15 posterior fossa and 4 spinal pediatric ependymomas by immunohistochemistry. Expression of high and low affinity neurotrophin receptors TrkA (NTRK1) and p75 (NGFR), pan-neuronal markers NeuN (RBFOX3) and synaptophysin, radial glial marker SOX9, adhesion molecules CD56 (NCAM) and CD44, junctional protein connexin 43 (GJA1), glial fibrillary acidic protein (GFAP), epithelial membrane antigen and proliferation associated antigen Ki-67 were evaluated in a semi-quantitative or quantitative (Ki-67 and NeuN-index) fashion. We found p75 and NeuN to be expressed at significantly higher levels in supratentorial versus infratentorial tumors and GFAP to be expressed at significantly higher levels in infratentorial lesions. In conclusion, immunohistochemical expression of p75, NeuN and GFAP differed in ependymomas depending on tumor topography supporting the view of divergent cells of origin. However, because of the small sample size the results are of preliminary nature and replication in a larger cohort would be desirable.
